This invention relates to a medical tube and a process for producing the same. More particularly, it relates to a medical tube having excellent compatibility with blood, particularly suited for an artificial blood vessel, and a process for producing the same.
Conventionally known process for producing medical tubes comprising thermoplastic high molecular weight compounds may include a process in which a high molecular weight compound is heat-melted, followed by extrusion (hereinafter called a "melt extrusion process"); a process in which a round rod-shaped mold is repeatedly dipped in a polymer solution until a polymer layer of a desired thickness is formed on it (hereinafter called a "dip process"); and a, process in which a solution comprising a high molecular weight compound is extruded from an annular orifice while an inside solidifying solution is extruded from the center of the annular orifice, and the whole is dipped in an outside solidifying solution (Japanese Unexamined Patent Publication No. 188164/1985).
However, any of these process may not obtain medical tubes that can exhibit the compatibility with blood with good reproducibility and for a long period of time, and there has been available no product that can be satisfactorily used particularly in artificial blood vessels having an inner diameter of 6 mm of less.
Specifically, the tubes obtained by the melt extrusion process may form smooth inner and outer faces, whereby the the wall of a tube may be so dense that it can not be freely controlled. Also, as a matter of course, they may have practically a great disadvantage that a needle can run through them only with difficulty at the time of suturing. Application of such tubes in such use as in artificial blood vessels for which a long term compatibility with the blood and surrounding tissue is required, may not give any desired results even if there are used materials such as polyurethane and polyurethane urea having excellent antithrombotic properties. In other words, with a prolonged period of transplantation, such tubes may turn limy with lapse of time to form as a result a large quantity of thrombi around them. It is also known that application of such tubes having a smooth inner face as artificial blood vessels may result in no stable take on the inner face of an artificial blood vessel, of the intimal tissue extending from a cut end of the blood vessel on the side of the living body, to cause the peeling, and therefore the flow of blood may be disturbed at that portion to produce thrombi, which thrombi may again grow into tissue to bring about hypertrophy of an intima.
The dip process may result in not only a low dimensional precision with an uneven wall thickness, but also a multi-layered wall structure, which can not be freely controlled with good reproducibility. Specifically, since it is impossible to uniformly control the evaporation of a solvent in the polyurethane solution applied on the mold for every dipping, the products may lack structural uniformity and those having high reliability can not be obtained.
The process disclosed in Japanese Unexamined Patent Publication No. 188164/1985 is characterized in that the solidification of the solution of a high molecular compound is carried out substantially from both sides of the inner face and outer face,, but otherwise has no difference at all from the conventional process for producing a hollow fibrous membrane, and can only produce a tube having skin layers on both of the faces since the solidification may proceed from the inside and outside of the tube. This process also requires a long period of time until the solidification reaches the state in which no deformation of the tube may occur. Accordingly, if a tube of large inner diameter is attempted to be produced, which may have poor shape stability, this process may have a disadvantage that deformation or ununiform solidification may readily occur in the course of taking-off, actually that a molded tube, having diameter more than 1 to 2 mm, may become oval.
For an artificial blood vessel having inner diameter of 7 mm or less, what is important is the coaptability with a living blood vessel, and delicate control of the properties is indispensable for improving the patency results. Especially, suitable flexibility is required in order for the inside of a living blood vessel and that of an artificial blood vessel to be smoothly joined each other at the time of suturing. Further, readiness in running-through of a suturing needle can improve the suturing performance, giving a great influence to the patency results. In other words, a good anastomotic performance is very important for making the flow path at a junction to a living blood vessel to have a desired shape. Properties also fundamentally necessary for the artificial blood vessels, which are used semipermanently, are such that a wall membrane must be as a matter of course endurable to the pulsational load by blood pressure to be applied 100,000 or more times a day, and also that a suture at which the stress may centralize may not be gradually dialated or broken.
There have been conventionally used artificial blood vessels produced by drawing polytetrafluoroethylene molded into a tube to have finely fibrous structure, which have been improved in the antithrombotic properties as compared with an artificial blood vessel produced by providing folds on a tube comprising woven polyester fiber. However, these not only have problems that a needle can run through only with difficulty and bleeding from needle holes may occur, but also have room for improvement in the coaptability with a living blood vessel.
In artificial blood vessels having inner diameter of 7 mm or less, particularly 6 mm or less, nothing has been available that can be used with clinically satisfactory patency results. Only a product obtained by making porous the above polytetrafluoroethylene has been used for limited purposes, which, however, shows unsatisfactory results in respect of the patent degree for more than one year. Thus, development of an artificial blood vessel having better patency has been sought after. In order to improve the patency results, it is first necessary and indispensable to improve the antithrombotic properties of a material. Further, the artificial blood vessel must be endowed with the above mechanical properties required as an artificial blood vessel. Next, it must retain the tube wall structure having excellent patency over a long term. Many experimental data have showed that the artificial blood vessel having the fine structure can not maintain the patent state for a long period of time as mentioned above. In particular, the intima growing at the inner face can not be stably retained, and may be repeatedly grown and peeled because of the blood flow or bending. Particularly at the junction to a living blood vessel, panni may abnormally grow, which may cause disturbance of blood flow, so that there may occur the growth of thrombi, which may gradually grow into tissue, resulting in the construction at the anastomosed portions. In order to achieve the stable take of intima, it is preferred that the inner face is provided with no skin layer and has concaves of 1 to 100 microns, preferably 3 to 20 microns, in diameter, and at the same time the concaves are open to the vacuole in the inside of a tube wall. Accordingly, the artificial blood vessel having the structure that the inner face is provided with no skin layer can not be produced by the known process in which the solidification is carried out from both of the inner face and outer face with use of an annular orifice.
As a process to avoid this problem, a proposal has been disclosed, for example, in Japanese Unexamined Patent Publication No. 188165/1985. That is a process in which a tube is molded while mixing a pore-forming agent in a solution, followed by removing the agent according to any suitable means to prevent a dense skin layer being formed on the inner face. This process, however, may be accompanied with a substantial disadvantage that not only the steps may be made very complicated but also the porosity of a blood vessel may become higher. Namely, the tube wall as a whole may become porous to cause exudation of plasma and bring about a complication such as seroma to worsen the prognosis. Similar phenomenon may frequently occur in the above mentioned artificial blood vessel made of polytetrafluoroethylene, thereby causing an infectious disease to necessarily require re-transplantation of the vessel, as well known. Needless to say, if on the other hand a pore-forming agent that may not cause any leakage of blood cell components from the tube wall is used, no stable take of tissue can be expected in the inner face of the artificial blood vessel.
It is preferable for an artificial blood vessel to have holes opened to the inside of a tube wall so that the stable take of intima on the inner face may be promoted, and at the same time have such dense structure on its outer face that may not allow not only blood cells but also plasma to pass therethrough. In addition to such a structural factor, it is necessary for an artificial blood vessel to be formed by use of a material that may have mechanically sufficient strength, may have substantial antithrombotic properties that can suppress the initial thrombus to a smaller quantity, and may not cause any strong histionic reaction or deterioration due to biodegradation even after a long term transplantation in a living body.
In order to eliminate the above-mentioned disadvantages pertaining to the conventional medical tubes, the present inventors have made intensive studies. As a result, they have succeeded in producing a medical tube having excellent compatibility with blood, particularly an artificial blood vessel having excellent patency. Thus the present invention has been accomplished.